Experimental Alzheimer’s drugs, particularly the recently approved anti-amyloid therapies like lecanemab (Leqembi) and donanemab (Kisunla), have shown some ability to slow disease progression in early-stage patients but come with significant risks and modest clinical benefits that have sparked debate about whether they might actually make some patients worse[2][5].
These drugs work by targeting amyloid plaques—sticky protein deposits in the brain long associated with Alzheimer’s disease. While they effectively reduce amyloid buildup, the clinical improvements observed are often subtle and barely noticeable even to trained neurologists[3]. Moreover, these treatments carry serious side effects, including brain swelling (amyloid-related imaging abnormalities or ARIA) and small brain bleeds, which in rare cases can be severe enough to cause seizures or death[2][5]. Patients with the APOE e4 gene variant, which increases Alzheimer’s risk, appear more susceptible to these complications, prompting FDA recommendations for genetic testing and regular brain MRI monitoring during treatment[2].
The controversy extends beyond side effects. Some experts question the overall effectiveness of these drugs, given their high cost and the limited degree of cognitive improvement they provide. For example, French and UK health authorities have expressed skepticism about reimbursing or recommending these treatments due to insufficient evidence of meaningful benefit relative to risks and expense[5]. Real-world data show that while lecanemab can be administered safely, it requires frequent MRI scans to detect potentially dangerous brain swelling early, adding to the treatment burden[6].
Beyond anti-amyloid therapies, other experimental approaches are being explored. Some researchers are shifting focus to neurofibrillary tangles—twisted filaments of tau protein that are also a hallmark of Alzheimer’s and may be more closely linked to cognitive decline. Drugs targeting tau formation are in clinical trials, and there is interest in developing vaccines to prevent tangle formation, potentially offering new avenues for treatment[3].
Other medications, such as the antidepressant vortioxetine, have been tested for cognitive and mood improvements in Alzheimer’s patients with depression. However, results are mixed. A 2022 study found vortioxetine did not significantly reduce depressive symptoms or cognitive impairment compared to placebo, though it was generally well tolerated[1].
Some drugs like levetiracetam have been investigated for their potential to slow cognitive decline, but so far, evidence remains inconclusive, with some analyses suggesting possible benefits in specific subgroups but no broad efficacy[4].
In summary, while experimental Alzheimer’s drugs have introduced hope by targeting underlying disease mechanisms, their modest benefits, serious side effects, and high costs raise concerns that in some cases, these treatments might worsen patient outcomes or quality of life. Ongoing research continues to seek safer, more effective therapies, including those targeting tau protein and other novel pathways[3][5].
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Sources:
[1] https://www.liveinhomecare.com/alzheimers-patients-linked-to-greater-cognitive-and-mood-improvements-due-to-antidepressant-vortioxetine/alzheimers/
[2] https://www.liveinhomecare.com/alzheimers-treatments-whats-coming/alzheimers/
[3] https://med.stanford.edu/news/insights/2025/09/rethinking-alzheimers-tau-protein.html
[4] https://www.nia.nih.gov/sites/default/files/20
